Semin Respir Crit Care Med 2007; 28(6): 662-671
DOI: 10.1055/s-2007-996413
© Thieme Medical Publishers

Optimizing Therapy for Acinetobacter baumannii

Anton Y. Peleg1 , 2
  • 1Division of Infectious Diseases, Beth Israel Deaconess Medical Center
  • 2Harvard Medical School, Boston, Massachusetts
Further Information

Publication History

Publication Date:
20 December 2007 (online)

ABSTRACT

Acinetobacter baumannii is a highly resilient, gram-negative coccobacillus that thrives within the unique and complex ecological setting of an intensive care unit. This evolving pathogen has now surpassed human capacity to create new antimicrobials, and has led physicians into a concerning era for hospital-acquired infections. This review presents the available evidence on the therapeutic strategies for A. baumannii infection, with a particular focus on clinical human data. The utility of existing and older antimicrobials such as sulbactam and the polymyxins are explored, as well as, the potential role of newer agents such as tigecycline. Other important adjunctive strategies such as pharmacodynamic target attainment and infection control implementation are briefly discussed. It is now clear that new antimicrobials with unique mechanisms of action are urgently required to combat the rising trends seen globally with drug-resistant A. baumannii.

REFERENCES

  • 1 Donskey C J. Antibiotic regimens and intestinal colonization with antibiotic-resistant gram-negative bacilli.  Clin Infect Dis. 2006;  43(Suppl 2) S62-S69
  • 2 Wendt C, Dietze B, Dietz E, Ruden H. Survival of Acinetobacter baumannii on dry surfaces.  J Clin Microbiol. 1997;  35 1394-1397
  • 3 Wisplinghoff H, Schmitt R, Wohrmann A, Stefanik D, Seifert H. Resistance to disinfectants in epidemiologically defined clinical isolates of Acinetobacter baumannii .  J Hosp Infect. 2007;  66 174-181
  • 4 Villegas M V, Hartstein A I. Acinetobacter outbreaks, 1977-2000.  Infect Control Hosp Epidemiol. 2003;  24 284-295
  • 5 Abbo A, Navon-Venezia S, Hammer-Muntz O, Krichali T, Siegman-Igra Y, Carmeli Y. Multidrug-resistant Acinetobacter baumannii .  Emerg Infect Dis. 2005;  11 22-29
  • 6 Coelho J M, Turton J F, Kaufmann M E et al.. Occurrence of carbapenem-resistant Acinetobacter baumannii clones at multiple hospitals in London and Southeast England.  J Clin Microbiol. 2006;  44 3623-3627
  • 7 Dalla-Costa L M, Coelho J M, Souza H A et al.. Outbreak of carbapenem-resistant Acinetobacter baumannii producing the OXA-23 enzyme in Curitiba, Brazil.  J Clin Microbiol. 2003;  41 3403-3406
  • 8 Hsueh P R, Teng L J, Chen C Y et al.. Pandrug-resistant Acinetobacter baumannii causing nosocomial infections in a university hospital, Taiwan.  Emerg Infect Dis. 2002;  8 827-832
  • 9 Landman D, Quale J M, Mayorga D et al.. Citywide clonal outbreak of multiresistant Acinetobacter baumannii and Pseudomonas aeruginosa in Brooklyn, NY: the preantibiotic era has returned.  Arch Intern Med. 2002;  162 1515-1520
  • 10 Peleg A Y, Franklin C, Bell J M, Spelman D W. Emergence of carbapenem resistance in Acinetobacter baumannii recovered from blood cultures in Australia.  Infect Control Hosp Epidemiol. 2006;  27 759-761
  • 11 Scott P, Deye G, Srinivasan A et al.. An outbreak of multidrug-resistant Acinetobacter baumannii-calcoaceticus complex infection in the US military health care system associated with military operations in Iraq.  Clin Infect Dis. 2007;  44 1577-1584
  • 12 Van Looveren M, Goossens H. Antimicrobial resistance of Acinetobacter spp. in Europe.  Clin Microbiol Infect. 2004;  10 684-704
  • 13 Abbott A. Medics braced for fresh superbug.  Nature. 2005;  436 758
  • 14 Hawley J S, Murray C K, Griffith M E et al.. Susceptibility of Acinetobacter strains isolated from deployed U.S. military personnel.  Antimicrob Agents Chemother. 2007;  51 376-378
  • 15 Spellberg B, Powers J H, Brass E P, Miller L G, Edwards Jr J E. Trends in antimicrobial drug development: implications for the future.  Clin Infect Dis. 2004;  38 1279-1286
  • 16 Wenzel R P. The antibiotic pipeline: challenges, costs, and values.  N Engl J Med. 2004;  351 523-526
  • 17 Talbot G H, Bradley J, Edwards Jr J E, Gilbert D, Scheld M, Bartlett J G. Bad bugs need drugs: an update on the development pipeline from the Antimicrobial Availability Task Force of the Infectious Diseases Society of America.  Clin Infect Dis. 2006;  42 657-668
  • 18 National Institutes of Health .Partnerships to Improve Diagnosis and Treatment of Selected Drug-Resistant Healthcare-Associated Infections (U01). RFA-AI-06-036
  • 19 Gaynes R, Edwards J R. Overview of nosocomial infections caused by gram-negative bacilli.  Clin Infect Dis. 2005;  41 848-854
  • 20 Halstead D C, Abid J, Dowzicky M J. Antimicrobial susceptibility among Acinetobacter calcoaceticus-baumannii complex and Enterobacteriaceae collected as part of the Tigecycline Evaluation and Surveillance Trial.  J Infect. 2007;  55 49-57
  • 21 Rhomberg P R, Fritsche T R, Sader H S, Jones R N. Clonal occurrences of multidrug-resistant gram-negative bacilli: report from the Meropenem Yearly Susceptibility Test Information Collection Surveillance Program in the United States (2004).  Diagn Microbiol Infect Dis. 2006;  54 249-257
  • 22 Jeon B C, Jeong S H, Bae I K et al.. Investigation of a nosocomial outbreak of imipenem-resistant Acinetobacter baumannii producing the OXA-23 beta-lactamase in Korea.  J Clin Microbiol. 2005;  43 2241-2245
  • 23 Pascual A, Perea E, Alvarez M et al.. The Meropenem Yearly Susceptibility Test Information Collection antimicrobial susceptibility program in Spain: a 5-year analysis.  Diagn Microbiol Infect Dis. 2007;  57 195-200
  • 24 Playford E G, Craig J C, Iredell J R. Carbapenem-resistant Acinetobacter baumannii in intensive care unit patients: risk factors for acquisition, infection and their consequences.  J Hosp Infect. 2007;  65 204-211
  • 25 Mulin B, Talon D, Viel J F et al.. Risk factors for nosocomial colonization with multiresistant Acinetobacter baumannii .  Eur J Clin Microbiol Infect Dis. 1995;  14 569-576
  • 26 Carbonne A, Naas T, Blanckaert K et al.. Investigation of a nosocomial outbreak of extended-spectrum beta-lactamase VEB-1-producing isolates of Acinetobacter baumannii in a hospital setting.  J Hosp Infect. 2005;  60 14-18
  • 27 Husni R N, Goldstein L S, Arroliga A C et al.. Risk factors for an outbreak of multi-drug-resistant Acinetobacter nosocomial pneumonia among intubated patients.  Chest. 1999;  115 1378-1382
  • 28 Scerpella E G, Wanger A R, Armitige L, Anderlini P, Ericsson C D. Nosocomial outbreak caused by a multiresistant clone of Acinetobacter baumannii: results of the case-control and molecular epidemiologic investigations.  Infect Control Hosp Epidemiol. 1995;  16 92-97
  • 29 Villers D, Espaze E, Coste-Burel M et al.. Nosocomial Acinetobacter baumannii infections: microbiological and clinical epidemiology.  Ann Intern Med. 1998;  129 182-189
  • 30 Corbella X, Montero A, Pujol M et al.. Emergence and rapid spread of carbapenem resistance during a large and sustained hospital outbreak of multiresistant Acinetobacter baumannii .  J Clin Microbiol. 2000;  38 4086-4095
  • 31 del Mar Tomas M, Cartelle M, Pertega S et al.. Hospital outbreak caused by a carbapenem-resistant strain of Acinetobacter baumannii: patient prognosis and risk-factors for colonisation and infection.  Clin Microbiol Infect. 2005;  11 540-546
  • 32 Lee S O, Kim N J, Choi S H et al.. Risk factors for acquisition of imipenem-resistant Acinetobacter baumannii: a case-control study.  Antimicrob Agents Chemother. 2004;  48 224-228
  • 33 Kaye K S, Harris A D, Samore M, Carmeli Y. The case-case-control study design: addressing the limitations of risk factor studies for antimicrobial resistance.  Infect Control Hosp Epidemiol. 2005;  26 346-351
  • 34 Blot S, Vandewoude K, Colardyn F. Nosocomial bacteremia involving Acinetobacter baumannii in critically ill patients: a matched cohort study.  Intensive Care Med. 2003;  29 471-475
  • 35 Garcia-Garmendia J L, Ortiz-Leyba C, Garnacho-Montero J, Jimenez-Jimenez F J, Monterrubio-Villar J, Gili-Miner M. Mortality and the increase in length of stay attributable to the acquisition of Acinetobacter in critically ill patients.  Crit Care Med. 1999;  27 1794-1799
  • 36 Garnacho J, Sole-Violan J, Sa-Borges M, Diaz E, Rello J. Clinical impact of pneumonia caused by Acinetobacter baumannii in intubated patients: a matched cohort study.  Crit Care Med. 2003;  31 2478-2482
  • 37 Grupper M, Sprecher H, Mashiach T, Finkelstein R. Attributable mortality of nosocomial Acinetobacter bacteremia.  Infect Control Hosp Epidemiol. 2007;  28 293-298
  • 38 Falagas M E, Bliziotis I A, Siempos I I. Attributable mortality of Acinetobacter baumannii infections in critically ill patients: a systematic review of matched cohort and case-control studies.  Crit Care. 2006;  10 R48
  • 39 Sunenshine R H, Wright M O, Maragakis L L et al.. Multidrug-resistant Acinetobacter infection mortality rate and length of hospitalization.  Emerg Infect Dis. 2007;  13 97-103
  • 40 Falagas M E, Kasiakou S K, Rafailidis P I, Zouglakis G, Morfou P. Comparison of mortality of patients with Acinetobacter baumannii bacteraemia receiving appropriate and inappropriate empirical therapy.  J Antimicrob Chemother. 2006;  57 1251-1254
  • 41 Falagas M E, Bliziotis I A. Pandrug-resistant gram-negative bacteria: the dawn of the post-antibiotic era?.  Int J Antimicrob Agents. 2007;  29 630-636
  • 42 Wood G C, Hanes S D, Boucher B A, Croce M A, Fabian T C. Tetracyclines for treating multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia.  Intensive Care Med. 2003;  29 2072-2076
  • 43 Levin A S. Multiresistant Acinetobacter infections: a role for sulbactam combinations in overcoming an emerging worldwide problem.  Clin Microbiol Infect. 2002;  8 144-153
  • 44 Brauers J, Frank U, Kresken M, Rodloff A C, Seifert H. Activities of various beta-lactams and beta-lactam/beta-lactamase inhibitor combinations against Acinetobacter baumannii and Acinetobacter DNA group 3 strains.  Clin Microbiol Infect. 2005;  11 24-30
  • 45 Higgins P G, Wisplinghoff H, Stefanik D, Seifert H. In vitro activities of the beta-lactamase inhibitors clavulanic acid, sulbactam, and tazobactam alone or in combination with beta-lactams against epidemiologically characterized multidrug-resistant Acinetobacter baumannii strains.  Antimicrob Agents Chemother. 2004;  48 1586-1592
  • 46 Urban C, Go E, Mariano N et al.. Effect of sulbactam on infections caused by imipenem-resistant Acinetobacter calcoaceticus biotype anitratus .  J Infect Dis. 1993;  167 448-451
  • 47 Corbella X, Ariza J, Ardanuy C et al.. Efficacy of sulbactam alone and in combination with ampicillin in nosocomial infections caused by multiresistant Acinetobacter baumannii .  J Antimicrob Chemother. 1998;  42 793-802
  • 48 Wood G C, Hanes S D, Croce M A, Fabian T C, Boucher B A. Comparison of ampicillin-sulbactam and imipenem-cilastatin for the treatment of Acinetobacter ventilator-associated pneumonia.  Clin Infect Dis. 2002;  34 1425-1430
  • 49 Valcke Y J, Rosseel M T, Pauwels R A, Bogaert M G, Van der Straeten M E. Penetration of ampicillin and sulbactam in the lower airways during respiratory infections.  Antimicrob Agents Chemother. 1990;  34 958-962
  • 50 Choi J Y, Kim C O, Park Y S et al.. Comparison of efficacy of cefoperazone/sulbactam and imipenem/cilastatin for treatment of Acinetobacter bacteremia.  Yonsei Med J. 2006;  47 63-69
  • 51 Cisneros J M, Reyes M J, Pachon J et al.. Bacteremia due to Acinetobacter baumannii: epidemiology, clinical findings, and prognostic features.  Clin Infect Dis. 1996;  22 1026-1032
  • 52 Jellison T K, McKinnon P S, Rybak M J. Epidemiology, resistance, and outcomes of Acinetobacter baumannii bacteremia treated with imipenem-cilastatin or ampicillin-sulbactam.  Pharmacotherapy. 2001;  21 142-148
  • 53 Smolyakov R, Borer A, Riesenberg K et al.. Nosocomial multi-drug resistant Acinetobacter baumannii bloodstream infection: risk factors and outcome with ampicillin-sulbactam treatment.  J Hosp Infect. 2003;  54 32-38
  • 54 Jimenez-Mejias M E, Pachon J, Becerril B, Palomino-Nicas J, Rodriguez-Cobacho A, Revuelta M. Treatment of multidrug-resistant Acinetobacter baumannii meningitis with ampicillin/sulbactam.  Clin Infect Dis. 1997;  24 932-935
  • 55 Levin A S, Levy C E, Manrique A E, Medeiros E A, Costa S F. Severe nosocomial infections with imipenem-resistant Acinetobacter baumannii treated with ampicillin/sulbactam.  Int J Antimicrob Agents. 2003;  21 58-62
  • 56 Foulds G. Pharmacokinetics of sulbactam/ampicillin in humans: a review.  Rev Infect Dis. 1986;  8(Suppl 5) S503-S511
  • 57 Meyers B R, Wilkinson P, Mendelson M H, Walsh S, Bournazos C, Hirschman S Z. Pharmacokinetics of ampicillin-sulbactam in healthy elderly and young volunteers.  Antimicrob Agents Chemother. 1991;  35 2098-2101
  • 58 Betrosian A P, Frantzeskaki F, Xanthaki A, Georgiadis G. High-dose ampicillin-sulbactam as an alternative treatment of late-onset VAP from multidrug-resistant Acinetobacter baumannii .  Scand J Infect Dis. 2007;  39 38-43
  • 59 Rodriguez-Hernandez M J, Cuberos L, Pichardo C et al.. Sulbactam efficacy in experimental models caused by susceptible and intermediate Acinetobacter baumannii strains.  J Antimicrob Chemother. 2001;  47 479-482
  • 60 Tong W, Wang R, Chai D, Li Z, Pei F. In vitro activity of cefepime combined with sulbactam against clinical isolates of carbapenem-resistant Acinetobacter spp.  Int J Antimicrob Agents. 2006;  28 454-456
  • 61 Song J Y, Kee S Y, Hwang I S et al.. In vitro activities of carbapenem/sulbactam combination, colistin, colistin/rifampicin combination and tigecycline against carbapenem-resistant Acinetobacter baumannii .  J Antimicrob Chemother. 2007;  60 317-322
  • 62 Ko W C, Lee H C, Chiang S R et al.. In vitro and in vivo activity of meropenem and sulbactam against a multidrug-resistant Acinetobacter baumannii strain.  J Antimicrob Chemother. 2004;  53 393-395
  • 63 Savov E, Chankova D, Vatcheva R, Dinev N. In vitro investigation of the susceptibility of Acinetobacter baumannii strains isolated from clinical specimens to ampicillin/sulbactam alone and in combination with amikacin.  Int J Antimicrob Agents. 2002;  20 390-392
  • 64 Appleman M D, Belzberg H, Citron D M et al.. In vitro activities of nontraditional antimicrobials against multiresistant Acinetobacter baumannii strains isolated in an intensive care unit outbreak.  Antimicrob Agents Chemother. 2000;  44 1035-1040
  • 65 Wolff M, Joly-Guillou M L, Farinotti R, Carbon C. In vivo efficacies of combinations of beta-lactams, beta-lactamase inhibitors, and rifampin against Acinetobacter baumannii in a mouse pneumonia model.  Antimicrob Agents Chemother. 1999;  43 1406-1411
  • 66 Markou N, Apostolakos H, Koumoudiou C et al.. Intravenous colistin in the treatment of sepsis from multiresistant gram-negative bacilli in critically ill patients.  Crit Care. 2003;  7 R78-R83
  • 67 Michalopoulos A S, Tsiodras S, Rellos K, Mentzelopoulos S, Falagas M E. Colistin treatment in patients with ICU-acquired infections caused by multiresistant gram-negative bacteria: the renaissance of an old antibiotic.  Clin Microbiol Infect. 2005;  11 115-121
  • 68 Levin A S, Barone A A, Penco J et al.. Intravenous colistin as therapy for nosocomial infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii .  Clin Infect Dis. 1999;  28 1008-1011
  • 69 Ouderkirk J P, Nord J A, Turett G S, Kislak J W. Polymyxin B nephrotoxicity and efficacy against nosocomial infections caused by multiresistant gram-negative bacteria.  Antimicrob Agents Chemother. 2003;  47 2659-2662
  • 70 Sobieszczyk M E, Furuya E Y, Hay C M et al.. Combination therapy with polymyxin B for the treatment of multidrug-resistant gram-negative respiratory tract infections.  J Antimicrob Chemother. 2004;  54 566-569
  • 71 Reina R, Estenssoro E, Saenz G et al.. Safety and efficacy of colistin in Acinetobacter and Pseudomonas infections: a prospective cohort study.  Intensive Care Med. 2005;  31 1058-1065
  • 72 Garnacho-Montero J, Ortiz-Leyba C, Jimenez-Jimenez F J et al.. Treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP) with intravenous colistin: a comparison with imipenem-susceptible VAP.  Clin Infect Dis. 2003;  36 1111-1118
  • 73 Koomanachai P, Tiengrim S, Kiratisin P, Thamlikitkul V. Efficacy and safety of colistin (colistimethate sodium) for therapy of infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii in Siriraj Hospital, Bangkok, Thailand.  Int J Infect Dis. 2007;  11 402-406
  • 74 Kwa A L, Loh C, Low J G, Kurup A, Tam V H. Nebulized colistin in the treatment of pneumonia due to multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa .  Clin Infect Dis. 2005;  41 754-757
  • 75 Michalopoulos A, Kasiakou S K, Mastora Z, Rellos K, Kapaskelis A M, Falagas M E. Aerosolized colistin for the treatment of nosocomial pneumonia due to multidrug-resistant gram-negative bacteria in patients without cystic fibrosis.  Crit Care. 2005;  9 R53-R59
  • 76 Feeley T W, Du Moulin G C, Hedley-Whyte J, Bushnell L S, Gilbert J P, Feingold D S. Aerosol polymyxin and pneumonia in seriously ill patients.  N Engl J Med. 1975;  293 471-475
  • 77 Falagas M E, Bliziotis I A, Tam V H. Intraventricular or intrathecal use of polymyxins in patients with gram-negative meningitis: a systematic review of the available evidence.  Int J Antimicrob Agents. 2007;  29 9-25
  • 78 Ng J, Gosbell I B, Kelly J A, Boyle M J, Ferguson J K. Cure of multiresistant Acinetobacter baumannii central nervous system infections with intraventricular or intrathecal colistin: case series and literature review.  J Antimicrob Chemother. 2006;  58 1078-1081
  • 79 Tunkel A R, Hartman B J, Kaplan S L et al.. Practice guidelines for the management of bacterial meningitis.  Clin Infect Dis. 2004;  39 1267-1284
  • 80 Bukhary Z, Mahmood W, Al-Khani A, Al-Abdely H M. Treatment of nosocomial meningitis due to a multidrug resistant Acinetobacter baumannii with intraventricular colistin.  Saudi Med J. 2005;  26 656-658
  • 81 Kasiakou S K, Rafailidis P I, Liaropoulos K, Falagas M E. Cure of post-traumatic recurrent multiresistant gram-negative rod meningitis with intraventricular colistin.  J Infect. 2005;  50 348-352
  • 82 Giamarellos-Bourboulis E J, Xirouchaki E, Giamarellou H. Interactions of colistin and rifampin on multidrug-resistant Acinetobacter baumannii .  Diagn Microbiol Infect Dis. 2001;  40 117-120
  • 83 Manikal V M, Landman D, Saurina G, Oydna E, Lal H, Quale J. Endemic carbapenem-resistant Acinetobacter species in Brooklyn, New York: citywide prevalence, interinstitutional spread, and relation to antibiotic usage.  Clin Infect Dis. 2000;  31 101-106
  • 84 Timurkaynak F, Can F, Azap O K, Demirbilek M, Arslan H, Karaman S O. In vitro activities of non-traditional antimicrobials alone or in combination against multidrug-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii isolated from intensive care units.  Int J Antimicrob Agents. 2006;  27 224-228
  • 85 Yoon J, Urban C, Terzian C, Mariano N, Rahal J J. In vitro double and triple synergistic activities of polymyxin B, imipenem, and rifampin against multidrug-resistant Acinetobacter baumannii .  Antimicrob Agents Chemother. 2004;  48 753-757
  • 86 Tan T Y, Ng L S, Tan E, Huang G. In vitro effect of minocycline and colistin combinations on imipenem-resistant Acinetobacter baumannii clinical isolates.  J Antimicrob Chemother. 2007;  60 421-423
  • 87 Falagas M E, Rafailidis P I, Kasiakou S K, Hatzopoulou P, Michalopoulos A. Effectiveness and nephrotoxicity of colistin monotherapy vs. colistin-meropenem combination therapy for multidrug-resistant gram-negative bacterial infections.  Clin Microbiol Infect. 2006;  12 1227-1230
  • 88 Motaouakkil S, Charra B, Hachimi A et al.. Colistin and rifampicin in the treatment of nosocomial infections from multiresistant Acinetobacter baumannii .  J Infect. 2006;  53 274-278
  • 89 Petrosillo N, Chinello P, Proietti M F et al.. Combined colistin and rifampicin therapy for carbapenem-resistant Acinetobacter baumannii infections: clinical outcome and adverse events.  Clin Microbiol Infect. 2005;  11 682-683
  • 90 Gales A C, Jones R N, Sader H S. Global assessment of the antimicrobial activity of polymyxin B against 54 731 clinical isolates of gram-negative bacilli: report from the SENTRY antimicrobial surveillance programme (2001-2004).  Clin Microbiol Infect. 2006;  12 315-321
  • 91 Li J, Rayner C R, Nation R L et al.. Heteroresistance to colistin in multidrug-resistant Acinetobacter baumannii .  Antimicrob Agents Chemother. 2006;  50 2946-2950
  • 92 Rahal J J. Novel antibiotic combinations against infections with almost completely resistant Pseudomonas aeruginosa and Acinetobacter species.  Clin Infect Dis. 2006;  43(Suppl 2) S95-S99
  • 93 Chait R, Craney A, Kishony R. Antibiotic interactions that select against resistance.  Nature. 2007;  446 668-671
  • 94 Bonapace C R, White R L, Friedrich L V, Bosso J A. Evaluation of antibiotic synergy against Acinetobacter baumannii: a comparison with Etest, time-kill, and checkerboard methods.  Diagn Microbiol Infect Dis. 2000;  38 43-50
  • 95 Chang S C, Chen Y C, Luh K T, Hsieh W C. In vitro activities of antimicrobial agents, alone and in combination, against Acinetobacter baumannii isolated from blood.  Diagn Microbiol Infect Dis. 1995;  23 105-110
  • 96 Drago L, De Vecchi E, Nicola L, Colombo A, Guerra A, Gismondo M R. Activity of levofloxacin and ciprofloxacin in combination with cefepime, ceftazidime, imipenem, piperacillin-tazobactam and amikacin against different Pseudomonas aeruginosa phenotypes and Acinetobacter spp.  Chemotherapy. 2004;  50 202-210
  • 97 Ermertcan S, Hosgor M, Tunger O, Cosar G. Investigation of synergism of meropenem and ciprofloxacin against Pseudomonas aeruginosa and Acinetobacter strains isolated from intensive care unit infections.  Scand J Infect Dis. 2001;  33 818-821
  • 98 Joly-Guillou M L, Wolff M, Farinotti R, Bryskier A, Carbon C. In vivo activity of levofloxacin alone or in combination with imipenem or amikacin in a mouse model of Acinetobacter baumannii pneumonia.  J Antimicrob Chemother. 2000;  46 827-830
  • 99 Jung R, Husain M, Choi M K, Fish D N. Synergistic activities of moxifloxacin combined with piperacillin-tazobactam or cefepime against Klebsiella pneumoniae, Enterobacter cloacae, and Acinetobacter baumannii clinical isolates.  Antimicrob Agents Chemother. 2004;  48 1055-1057
  • 100 Roussel-Delvallez M, Wallet F, Delpierre F, Courcol R J. In vitro bactericidal effect of a beta-lactam + aminoglycoside combination against multiresistant Pseudomonas aeruginosa and Acinetobacter baumannii .  J Chemother. 1996;  8 365-368
  • 101 Sader H S, Rhomberg P R, Jones R N. In vitro activity of beta-lactam antimicrobial agents in combination with aztreonam tested against metallo-beta-lactamase-producing Pseudomonas aeruginosa and Acinetobacter baumannii .  J Chemother. 2005;  17 622-627
  • 102 Montero A, Ariza J, Corbella X et al.. Antibiotic combinations for serious infections caused by carbapenem-resistant Acinetobacter baumannii in a mouse pneumonia model.  J Antimicrob Chemother. 2004;  54 1085-1091
  • 103 Saballs M, Pujol M, Tubau F et al.. Rifampicin/imipenem combination in the treatment of carbapenem-resistant Acinetobacter baumannii infections.  J Antimicrob Chemother. 2006;  58 697-700
  • 104 Owen J, Darling I, Troy S, Cirincione B. Noncompartmental pharmacokinetics of tigecycline in patients with complicated skin and skin structure infections [abstract A-11]. In: Program and Abstracts of the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (Washington DC). Washington, DC; American Society for Microbiology 2004: 2
  • 105 Betriu C, Rodriguez-Avial I, Sanchez B A, Gomez M, Alvarez J, Picazo J J. In vitro activities of tigecycline (GAR-936) against recently isolated clinical bacteria in Spain.  Antimicrob Agents Chemother. 2002;  46 892-895
  • 106 Henwood C J, Gatward T, Warner M et al.. Antibiotic resistance among clinical isolates of Acinetobacter in the UK, and in vitro evaluation of tigecycline (GAR-936).  J Antimicrob Chemother. 2002;  49 479-487
  • 107 Peleg A Y, Potoski B A, Rea R et al.. Acinetobacter baumannii bloodstream infection while receiving tigecycline: a cautionary report.  J Antimicrob Chemother. 2007;  59 128-131
  • 108 Conte Jr J E, Golden J A, Kelly M G, Zurlinden E. Steady-state serum and intrapulmonary pharmacokinetics and pharmacodynamics of tigecycline.  Int J Antimicrob Agents. 2005;  25 523-529
  • 109 Jones M E. In-vitro profile of a new beta-lactam, ceftobiprole, with activity against methicillin-resistant Staphylococcus aureus .  Clin Microbiol Infect. 2007;  13(Suppl 2) 17-24
  • 110 Mushtaq S, Ge Y, Livermore D M. Comparative activities of doripenem versus isolates, mutants, and transconjugants of Enterobacteriaceae and Acinetobacter spp. with characterized beta-lactamases.  Antimicrob Agents Chemother. 2004;  48 1313-1319
  • 111 Mushtaq S, Warner M, Ge Y, Kaniga K, Livermore D M. In vitro activity of ceftaroline (PPI-0903M, T-91825) against bacteria with defined resistance mechanisms and phenotypes.  J Antimicrob Chemother. 2007;  60 300-311
  • 112 Jaruratanasirikul S, Sriwiriyajan S, Punyo J. Comparison of the pharmacodynamics of meropenem in patients with ventilator-associated pneumonia following administration by 3-hour infusion or bolus injection.  Antimicrob Agents Chemother. 2005;  49 1337-1339
  • 113 Kuti J L, Dandekar P K, Nightingale C H, Nicolau D P. Use of Monte Carlo simulation to design an optimized pharmacodynamic dosing strategy for meropenem.  J Clin Pharmacol. 2003;  43 1116-1123
  • 114 Li C, Kuti J L, Nightingale C H, Nicolau D P. Population pharmacokinetic analysis and dosing regimen optimization of meropenem in adult patients.  J Clin Pharmacol. 2006;  46 1171-1178
  • 115 Santos Filho L, Eagye K J, Kuti J L, Nicolau D P. Addressing resistance evolution in Pseudomonas aeruginosa using pharmacodynamic modelling: application to meropenem dosage and combination therapy.  Clin Microbiol Infect. 2007;  13 579-585
  • 116 Tam V H, Schilling A N, Neshat S, Poole K, Melnick D A, Coyle E A. Optimization of meropenem minimum concentration/MIC ratio to suppress in vitro resistance of Pseudomonas aeruginosa .  Antimicrob Agents Chemother. 2005;  49 4920-4927
  • 117 Harris A D, McGregor J C, Furuno J P. What infection control interventions should be undertaken to control multidrug-resistant gram-negative bacteria?.  Clin Infect Dis. 2006;  43(Suppl 2) S57-S61
  • 118 Chan P C, Huang L M, Lin H C et al.. Control of an outbreak of pandrug-resistant Acinetobacter baumannii colonization and infection in a neonatal intensive care unit.  Infect Control Hosp Epidemiol. 2007;  28 423-429
  • 119 Peleg A Y, Paterson D L. Multi-drug-resistant Acinetobacter: a threat to the antibiotic era.  Intern Med J. 2006;  36 479-482
  • 120 Pimentel J D, Low J, Styles K, Harris O C, Hughes A, Athan E. Control of an outbreak of multi-drug-resistant Acinetobacter baumannii in an intensive care unit and a surgical ward.  J Hosp Infect. 2005;  59 249-253
  • 121 Dellit T H, Owens R C, McGowan Jr J E et al.. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship.  Clin Infect Dis. 2007;  44 159-177
  • 122 American Thoracic Society; Infectious Diseases Society of America . Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.  Am J Respir Crit Care Med. 2005;  171 388-416
  • 123 Chastre J, Wolff M, Fagon J Y et al.. Comparison of 8 vs. 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial.  JAMA. 2003;  290 2588-2598

Anton Y PelegM.D. 

Division of Infectious Diseases

Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215

Email: apeleg@bidmc.harvard.edu

    >